Grant: Discovery Grants Program - Individual

Proteins and messenger RNA carry out their biological functions in the cell as macromolecules with a repertoire of structures available and with their stability depending on physiological and environmental conditions. Sequencing and structural data accumulated in public databases wait to be explored systematically to infer the factors of macromolecular dynamics and to generate new, experimentally testable hypotheses on protein and messenger RNA dynamics. The proposed research utilizes several modes of computational and high-throughput biology to discover novel determinants of transcript stabilities in the expressed genome of eukaryotic species, including humans. Messenger transcript stabilities are an important factor in gene regulation: Because transcripts have different binding affinities for interacting proteins, their lifetime and therefore availability for protein synthesis depends on the presence of sequence motifs and their presentation as either single-strand or base-paired local structures. The proposed research will capitalize on previous microarray-based research on the processing and stability of both coding and non-coding RNA and launch a comprehensive computational and systems biology investigation of sequence and structure motifs in the untranslated regions of messenger RNAs and their statistical associations with transcript fate in terms of lifetime, affinity to RNA-binding proteins and cytoplasmic localization. Generically, through the study of yeast as a model organism, and for gene regulation in two selected focal areas: immunology and oxidative metabolism, the research will include experimental collaborations and is expected to lead to new insights in posttranscriptional gene regulation with applications in basic biology, RNA-based biotechnology and RNAi-based gene therapy.